In general terms, the main research conducted in this proposal is directed toward a better understanding of the action of narcotic analgesics and the development of tolerance and physical dependence to these drugs using laboratory animals. More specifically, the proposal concerns: 1) the role of biogenic amines on narcotic tolerance and efficacy of narcotic antagonists, 2) N-demethylase activity in methadone-dependent rats, 3) effect of narcotics on the transport of amino acid precursors of putative neurotransmitters into the brain, 4) uptake of H3-etorphine by slices of various parts of the brain, 5) characterization of narcotic receptors in the guinea pig ileum and 6) characterization of the narcotic respiratory receptor. BIBLIOGRAPHIC REFERENCES: Tulunay, F. C. and Takemori, A. E.: The effect of morphine on the incorporation of H3-leucine into retinal proteins and subsequent axonal transport in the optic system of rats, Life Sci. 16:551-560, 1975. Huang, J. T. and Takemori, A.E.: Accumulation of methadone by the choroid plexus in vitro, Neuropharmacology 14:241-246, 1975.